Research Article Open Access

Youssef and Budoff, Angiol 2013, 1:2

http://dx.doi.org/10.4172/2329-9495.1000111
Review Article Open Access
Angiology: Open Access
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
Introduction
Atherosclerotic cardiovascular diseases are still the leading cause
of deaths in industrialized Countries and Coronary Artery Disease
(CAD) accounts for the majority of this toll [1]. Cardiac events are
typically caused by disruption of coronary plaques where plaque
rupture occurs in about two thirds of cases, while the remaining third
of cases are caused by plaque erosion with subsequent formation of
occluding thrombus [2]. Tus, a clinically relevant denition of a
rupture-prone (or what has been termed the vulnerable) plaque, is
a lesion that places a patient at risk for future major adverse cardiac
events, including death, myocardial infarction, or progressive angina.
On the other hand, the histopathological features that have been
associated with vulnerable plaques and defned them, include: 1) A large
eccentric necrotic lipid core, occupying approximately one-quarter of
the plaque area [3], 2) A thin fbrous cap (<65 m thick) [4], 3) Heavy
infltration by large number of infammatory cells (macrophages
and T cells) particularly at the shoulder region of the plaque [5], 4)
Spotty calcifcation, 5) Neovascularization due to proliferation of the
vasa vasora and formation of immature and leaky microvessels, with
subsequent rupture and intra-plaque hemorrhage [6], fnally, 6) In
contrast to eroded plaques, rupture-prone plaquesusually are non- or
mildly obstructive, yet the size of the plaque may be substantial due
to the phenomenon of positive remodeling [7]. Yet, some of these
aforementioned features, namely calcifcation and positive remodeling
are still controversial about their actual role in plaque stability.
Invasive coronary angiography, though presumably considered
as the gold standard for the diagnosis of CAD, is a mere luminogram
that focuses mainly on the stenosis severity rather than plaque
characteristics. Moreover, other traditional non-invasive stress tests
as stress echocardiography or myocardial perfusion imaging only help
detect hemodynamically signifcant lesions rather than non-obstructive
potentially vulnerable plaques.
Obstacles in detection of vulnerable plaques include their small
size and being localized within the rapidly moving coronary arteries.
In addition, plaque vulnerability is a dynamic process, a plaque that
appears rupture-prone today could rather be stable tomorrow, even
ruptured plaques do not always lead to coronary events as many
ruptures occur and heal silently. Terefore, there has been a growing
interest for detection and characterization of coronary atherosclerotic
plaques. Te aim of the present review paper is to shed some light
on diferent diagnostic modalities used for the assessment of plaque
vulnerability, with specifc focus on the Multi-Detector Computed
Tomography (MDCT) as an evolving tool in that feld with all its
strengths and limitations.
Imaging Modalities used for Assessment of Vulnerable
Plaques
Direct visualization of atherosclerotic plaques in vivo is the only
way forward for studying the natural history of atherosclerotic disease.
Te imaging techniques currently used are generally able to provide
adequate information on the lumen diameter reduction or its functional
signifcance. So, diferent imaging techniques; both invasive and non-
invasive, have been developed to reliably evaluate plaque composition
and identify its vulnerable features, thereby allow implementation of
treatment strategies to prevent adverse coronary events. Table 1 lists
diferent invasive and non-invasive imaging modalities with main
strengths and limitations.
In addition to being expensive and in need for specially trained
personnel, invasive techniques by their very nature, have a lower
level of patient acceptability than non-invasive modalities which may
provide a good alternative. Collectively, factors that characterize an
ideal non-invasive technique would include; patient-related factors:
1) wide range of clinical indications, 2) absence of ionizing radiation,
3) unnecessary administration of contrast media and 4) not precluded
by metallic devices or leads, and technical factors: 1) Rapid image
acquisition, 2) high temporal, spatial and contrast resolution, 3) ability
to provide both anatomic and metabolic information, and 4) accurate
and reproducible [26].
*Corresponding author: George Youssef, Los Angeles Biomedical Research
Institute, Harbor UCLA, 1124 West Carson Street, Torrance CA 90503, USA, Tel:
310-222-4107; Fax: 310-782-9652; E-mail: george.youssef@yahoo.com
Received May 25, 2013; Accepted July 26, 2013; Published July 28, 2013
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary
Angiography in the Detection of Vulnerable Plaque, Where Does it Stand Among
Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Copyright: 2013 Youssef G, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Abstract
Recently, there has been a growing interest in identifcation of coronary vulnerable plaques that are prone to
rupture; this potentially would help identify patients with higher risk of development of cardiac events. Recent advances
in cardiac imaging modalities have been successful in studying various plaque vulnerability features to variable
degrees, strengths and limitations. Computed Tomography Coronary Angiography (CTCA) has gained an increasing
popularity in studying plaque anatomy, morphology and composition by the virtue of its widespread availability and
non-invasiveness. CTCA has been validated against histology and IVUS with reasonable correlation; moreover,
some follow-up studies have shown a signifcant association to the development of acute coronary syndromes.
Nevertheless, attention should be paid to the whole patient big picture that includes other factors operating on other
extra-coronary axes that involve infammation, immunity, coagulation and neuroendocrine systems.
Role of Computed Tomography Coronary Angiography in the Detection of
Vulnerable Plaque, Where Does it Stand Among Others?
George Youssef* and Matthew Budoff
Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, California, USA
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it
Stand Among Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Page 2 of 8
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
Modality Mechanism Spatial resolution Strengths Limitations Relevant Studies
Invasive Modalities
Intravascular ultrasound
(IVUS) [8-11]
The intensity of the backscattered
signalis processed into gray scale
differs among different plaque
components
150 m
Provides information on
plaque anatomical features
and composition to lesser
extent [12]
-Invasiveness
-Limited temporal
resolution
-Limited spatial resolution
so cannot recognize thin
cap fbrotheroma (TCFA)
-Gray scale IVUS cannot
accurately differentiate
elements of plaque
composition
-Features of plaque
vulnerability include:
eccentric pattern,
echolucent core, positive
remodeling, presence of
thrombi, plaque length,
lumen narrowing and
spotty calcifcation [13,14]
IVUS-RF (radiofrequency)
analysis e.g. Virtual
histology (VH) [8-11]
RF data are more in direct
relation to the interaction of
ultrasound with tissue
100-200 m
-Ability to differentiate
between 4different tissue
types in plaques; dense
calcium, fbrous, fbro-fatty
and necrotic core [15]
-Identifcation of TCFA
-Invasiveness
-Limited spatial resolution
-When compared to
histology, sensitivity,
specifcity and predictive
accuracy of VH to
detect necrotic core,
a vulnerability feature
were 67%, 93% and 88%
respectively [16]
-PROSPECT study showed
a correlation between
presence of TCFA and
future major adverse
cardiac events (hazard
ratio: 3.35) [17,18]
Palpography
(intravascular
elastography)
[8,10]
Measures the local strain rate of
vessel wall and plaque (fbrous
plaques are stiffer than lipid-rich
ones) high strain regions denote
more vulnerable plaques
200-400 m
Identifcation of thin fbrous
caps
-Invasiveness
-Limited spatial resolution
-Cardiac motion
Human studies have
shown a strong correlation
between number of highly
deformable plaques
and both the clinical
presentation (ACS Vs.
stable patients) [18]
Intravascular MRI (IV-MRI)
[8]
Calculates the water diffusion
coeffcient: lipid-rich < fbrous
plaques
120 m
Detection of plaque
composition
-Invasiveness
There was a good
correlation between
MRI and histology with
sensitivity and specifcity of
100% and 89% [19]
Angioscopy [8-11]
Direct visualization of the
endothelial surface. The intensity
of the yellow color detected is
used for plaque characterization
200 m
Precise visualization of
plaque surface detecting
disrupted plaques (ulcers,
fssures)
-Invasiveness
-Limited
tissue penetration and
spatial resolution
Number of yellow plaques
were shown to be a strong
predictor of ACS [20]
Optical coherent
tomography (OCT) [8-11]
Light-based imaging, measures
the amplitude of backscattered
light (optical echoes) from a
sample as a function of time
delay
4-20 m
-Highest spatial resolution,
able to resolve thin fbrous
caps <65 m
-Only technique able to
detect eroded plaques
-Accurate detection of
plaque composition
-Invasiveness
-Limited tissue penetration
(1.25 mm). however, the
most relevant morphologic
fndings are
primarily localized within
the frst 500 m under
lumen surface
Second generation OCT
e.g. Optical Frequency
Domain Imaging has
shown a good potential to
defne plaque constituents
compared to histology [21]
Near Infrared spectroscopy
(NIRS) [8,10,11,22]
Different molecules
absorb and scatter
near-infrared light
differently allowing
for the chemical
characterization of
biological tissues
N/A
Detection of plaque
composition
-Invasiveness
-Limited tissue penetration
-Cardiac motion
When compared to
histology, sensitivity and
specifcity of NIRSto detect
lipid core, thin cap and
infammatory cellswere
77%-90%, and 89%-93%
respectively [23]
Thermography
[8,10]
Plaque infammation
and neoangiogenesis
produce heat measured at the
surface of the
plaque
500 m
Detection of plaque
infammation and
neoangiogenesis
-Invasiveness
-Limited tissue penetration
and spatial resolution
-Cooling effect of
blood underestimates
temperature differences
Thermal heterogeneity
has been correlated with
features of vulnerable
plaque like positive
remodeling [24]
Non-invasive modalities
MDCT
[8,10,25,26]
-Detects plaque morphology and
composition by measuring local
tissue attenuation
-Molecular imaging using new
contrast agents is under study
500 m
(200-300 m in
dual-source CT)
-Widely available
-Detection of lumen
narrowing accurately
-Detection of plaque
morphology and
composition (within limits)
-High spatial and temporal
resolution
-Ionizing Radiation
-Contrast agent
-Artifacts e.g. blooming
-Overlap in the attenuation
spectrum of non-calcifed
plaque components (lipid
and fbrous)
See later for details
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it
Stand Among Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Page 3 of 8
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
Systematic comparison between invasive and non-invasive
modalities for coronary plaque characterization in ex-vivo specimens
demonstrated that CTCA and IVUS are reasonably associated with
plaque composition and lesion grading according to histopathologic
fndings, while Optical Frequency Domain Imaging (a second
generation of OCT) was strongly associated.
Imaging features that were associated with advanced lesions were,
mixed plaque at CTCA, calcifcation at IVUS and lipid-rich plaque
at OFDI). Moreover, OFDI showed a better diagnostic accuracy
diferentiating early from advanced coronary lesions, with area under
the curve (AUC) of 0.8 compared to AUC of 0.63 and 0.68 for IVUS
and CTCA respectively [21].
Multi-detector Computed Tomography
First-generation scanners, or conventional CT, utilized a single
X-ray source and single X-ray detector cell. Over the past two decades
with the tremendous advances in technology, MDCT presented a
breakthrough in cardiac CT imaging technology by 1) increasing the
number of detector rows from 4 to 320 thus increasing the coverage
in the Z-axis up to 16 cm in a single heart beat with a single gantry
rotation, 2) speeding up the gantry rotation, enough to freeze the
cardiac motion by capturing images within the relatively brief period
of cardiac diastasis. the use of dual-source MDCT system has markedly
improved the temporal resolution to approximately 85 msec, resulting
in a shorter scan time and 3) decreasing the thickness of the detectors
to 0.5-0.625 mm thus increasing the spatial resolution to image sub-
millimeter structures. Tis has allowed more accurate and detailed
imaging of coronary plaques morphology and composition.
MDCT has caught up with coronary angiography, showing an
excellent diagnostic accuracy in diagnosis of obstructive CAD when
compared to coronary angiography as the gold standard. In a recent
meta-analysis of 188 studies (from 2004 to 2011), the mean sensitivity
and specifcity of MDCT were 97% and 87% respectively [31].
Role of MDCT in Detection of Vulnerable Plaque;
Morphology and Composition
Te potential for MDCT evaluation of coronary plaques is
enormous, given its noninvasive nature and its ability to evaluate
the entire coronary arterial tree in contrast to IVUS.MDCT can help
detect the suggested triad of the main features associated with plaque
vulnerability namely; positive remodeling, low attenuation (<30 HU),
and spotty calcications [32-35]. Other imaging phenomenon, that has
been reported to be pathologically related to thin cap fbrotheromais
the napkin ring sign, defned as the presence of a ring of high
attenuation around plaque; with a higher CT attenuation than those of
the adjacent plaque but no greater than 130 HU in order to diferentiate
from calcium depositions [36] (Figures 1 and 2).
Plaque morphology
Assessment of the plaque size rather than the luminal size is a more
logical approach especially in plaques that show substantial positive
remodeling, potentially indicating a higher risk for events than plaques
with lesser extent of remodeling. Motoyama et al. [35] calculated the
remodeling index and reported positive remodeling when the diameter
at the plaque site was at least 10% larger than reference segment, it was
shown that the frequency of positive remodeling among patients with
acute coronary syndrome (ACS) was signifcantly higher than those
with stable angina (87% Vs. 12%, P<0.0001)[35]. Similar fnding was
High resolution MRI
[8,10,25,26]
-Uses different contrast
weightings (T1, T2, proton-
density and time-of-fight) to
evaluate the biological features of
plaque components
-Molecular imagingusing specifc
agents like paramagnetic
nanoparticles targeting:
Fibrin: in plaque disruption and
thrombosis
Cellular markers as E-selectin
and vascular cellular adhesion
molecule (VCAM): in
infammation and Integrin v3
in angiogenesis
1 mm (improves to
350 m in carotids)
-Absence of ionizing
radiation
-High contrast resolution
(by nullifying the blood
signal from the lumen, by
using real time respiratory
navigated black blood fast
spin echo sequences)
-Contraindicated with
many intracardiac devices
-Cardiac motion
-Poor reproducibility
-Contrast agent
-Limited spatial
Resolution
-Time consuming
reconstruction techniques
Fayad et al reported
positive remodeling and
signifcant coronary wall
thickening in patients with
CAD compared to control
patients [27]
Nuclear imaging
(SPECT/PET)
[8,10, 25,26]
Molecular imagingtargeting
Macrophages: in infammation
using18F-Flurodeoxyglucose
(FDG)
Apoptotic cells: using Annexin V
Vasoconstricting peptides: using
18F-Endothelin-1 (ET-1)
PET: 4-5 mm
SPECT: 1-1.6 cm
Holds the potential for
superior cellular and
molecular imaging
compared to MDCT and
MRI
-Ionizing Radiation
-Cardiac motion
-Very limited spatial
and temporal resolution
renders coronary imaging
challenging
-Less availability for PET
-Myocardial FDG uptake
with PET
Tawakol et al
showed noticeable
correlation between
18
F-FDG-PET in vivo
signals and macrophage
content on histological
examination after carotid
endarterectomy [28]
Contrast-Enhanced
ultrasonography
[8,10,25]
-Acoustically active microbubbles
(3-4 m in diameter) that act as
pure intravascular tracers, when
exposed to ultrasound feld, they
produce a strong backscatter
signal and specifc nonlinear
signal that differentiates them
from surrounding tissues
-Molecular imaging; microbubbles
labeled monoclonal antibodies
targeting endothelial surface
molecules e.g VCAM-1
3-4 m
-Absence of ionizing
radiation
-High temporal and spatial
resolution
-Assessment of
neovasculature
-Limited spatial resolution
and penetration
-Limited application
to carotid rather than
coronary arteries
Enhancement of carotid
plaques has been
correlated with both
histopathology and clinical
presentation
[29,30]
Table 1: Characteristics of different imaging modalities used for detection of vulnerable plaques.
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it
Stand Among Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Page 4 of 8
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
confrmed when Pfederer et al. [37] showed a signifcantly higher
remodeling index in ACS patients when compared to those with stable
angina (1.6 0.4 Vs. 0.97 0.17, P<0.001) [37]. When validated against
IVUS, Te diagnostic accuracy of MDCT in detection of positive
remodeling was excellentwhere area under the curve was >0.9with
excellent sensitivity and specifcity of 100% and 90% respectively [38].
Interestingly, in a recent paper that used coronary artery simulation
models, vessel wall stress concentrations were always predicted to be
higher in the brous cap of plaques with positive remodeling compared
to those with negative remodeling independent of the brous cap and
the degree of stenosis [39].
Invasive coronary imaging is the gold standard for detection of
disrupted plaques, the angiographic hallmark of complex lesions was
characterized by Ambrose criteria including haziness, ulceration,
intraplaque dye penetration and intraluminal flling defects, these
features correlated with both histology and IVUS [40]. Tere are only
scant data regarding the ability of Computed Tomography Coronary
Angiography (CTCA) to identify features of plaque disruption;
ulceration and/orintraplaque dye penetration. When compared to
IVUS, MDCT was less accurate for the detection of plaque disruption
in coronary arteries; sensitivity 57%, specifcity 71% [41]. A more
recent study that used the invasive angiography as the gold standard,
MDCT has shown a good specifcity (82-95%) but modest to good
sensitivity (53%-58%). Te lower sensitivity is likely attributable to the
lower spatial resolution of CTCA compared with invasive angiography
and presence of plaque calcifcation [42].
On the other hand, in carotid arteries, the introduction of MDCT
did improve the detection of ulceration improving the sensitivity of
single slice CT from 60 to 87% and specifcity from 74 to 98% [43-46].
Plaque composition
By virtue of MDCT ability to measure local tissue attenuation,
MDCT also allows imaging of the vessel wall, potentially providing
insights into plaque composition rather than the physiology [47].
Identication of plaque composition is based on measuring the
attenuation coefcient which is displayed as a CT number relative to
the attenuation of water (0 Hounsfeld units HU) and air (1000 HU)
[48]. Calcifcations appear as hyperdense, fbrous tissue as isodense
and lipid core, intra-plaque hemorrhage and thrombus as hypodense.
However, using the absolute CT numbers to defne diferent plaque
constituents, especially of sof plaques, is infuenced by various factors
that could limit its accurate assessment, rendering the exact defnition
of low attenuation plaque values with the currently available techniques
more challenging. Tese factors include; attenuation of intracoronary
contrast medium, tube voltage, degree of stenosis, use of diferent
reconstruction flters [49]. Table 2 shows some studies that reported
CT attenuation values of various coronary plaque types in relation to
IVUS. Of note, the reported CT numbers showed signifcant diferences
in densities of plaque components, yet, with substantial overlap.
Coronary artery calcium (CAC) is defned as a hyper-attenuating
lesion >130 HU within an area of 3 pixels. Agatston score has been
widely used to quantify CAC scoreby multiplying the lesion area (mm
2
)
by a density factor (between 1 and 4) [54]. CAC score with its clinical
and prognostic implications will be discussed later.
Diferent classifcations of morphological patterns of calcifcation
have been used in previous reports, one classifcation was as: speckled
(calcifed nodules), fragmented (shell-like, linear, or wide, single
focus of calcium >2 mm in diameter), or difuse ( 5-mm segment
of continuous calcifcation) [55]. Calcifed nodules have been well
described on IVUS studies and identifed as a less common cause of

Figure 1: A straight-vessel view for the left anterior descending artery with a
proximal plaque. The vessel lumen is measured at the plaque site (B = 4mm)
as well as the proximal (A=3.4mm) and distal (C=3mm) reference segments
demonstrating positive remodeling.
Figure 2: Fig 2A shows a curved multi-planar reformation (MPR) image to the
left anterior descending artery with a proximal plaque. Figs 2B, C and D are
cross section images of the vessel at the plaque site, the criteria of plaque
vulnerability shown are: spotty calcifcation (arrow 1), low attenuation plaque,
ranging between 14-23 HU (arrow 2) and napkin ring sign (arrow 3).
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it
Stand Among Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Page 5 of 8
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
plaque disruption (2-7%). On CTCA, Calcifed nodules were observed
in association with only 6% of obstructive stenotic lesions (>50%),
whereas 44% of non-obstructive lesions showed this calcifcation
pattern [55].
Other studies described classifcation patterns as spotty and
dense calcication. Spotty calcifcation was defned and sub-classifed
according to their length on curved multiplanar reconstruction into:
small spotty (<1 mm), intermediate spotty (1-3 mm), and large spotty
calcications ( 3 mm). Dense calcications were dened as a plaque
with high CT density, completely calcied and with calcications
present bilateral on cross-sectional axial slices [33,56,57]. A recent
study, used high-resolution micro-computed tomography to identify
micro-calcifcations in the cap proper of 62 human coronary
fbroatheromas, it showed that micro-calcifcations were abundant in
lipid pools. However, those calcifcations observed in the brous caps
increased the risk of rupture by introducing a stress concentration
efect [58]. From the clinical viewpoint, this is highlighting the notion
that it is not the micro-calcifcations per se that are dangerous but their
locations in the cap.
When validating MDCT studies, both histology and IVUS have
been used as reference standard. Tough histology is a better reference
standard, IVUS is considered an accepted method for evaluation of the
coronary arteries, where histology cannot be obtained.
When compared to histology, MDCT has shown a strong
correlation for detection of calcifcation and fbrous tissue, while
correlation was moderate for the detection of the amount of lipid core
and fbrous tissue when compared to IVUS (Table 3). Also, MDCT
could accurately detect calcifed plaques with excellent sensitivity
and specifcity reaching 100% in a carotid study by Wintermark et al.
[46]; however, the detection of calcifcations alone is not enough for
the assessment of vulnerable plaques. As previously mentioned, due
to some technical limitations, the sof tissue contrast of CT is low,
resulting in a moderate diagnostic accuracy with a sensitivity range of
(62%-94%) and specifcity range of (74%-100%) [41,45,46].
Similar to positive remodeling, low attenuation plaque value
(defned as <30 HU) and spotty calcifcation (defned as <3mm in size)
were signifcantly more frequent in ACS patients than in stable disease
(79% Vs. 9%, p<0.0001 and 63% Vs. 21%, p=0.0005 respectively) [35].
Te concomitant presence of the 3 high risk features was associated
with a high positive predictive value for culprit lesions in ACS (95%)
while their absence showed a high negative predictive value (100%)
[35]. Of note, in a study where dual source CTCA was used, both spotty
calcifcation and napkin ring signs were exclusive to ACS patients [37].
Te role of calcication in determining the stability of individual
plaque and its likelihood to rupture causing an event is still controversial.
Some authors have assumed calcifcation to be protective against
plaque rupture and a sign of healed plaques, especially that plaques with
erosions (a less frequent mechanism of acute coronary syndromes) are
ofen not calcied [65]. On the other hand, others have shown that
the presence of small hard-rock calcium adjacent to sof tissues create
forces that contribute to plaque instability and coronary events [66-69].
In the majority of patients with acute coronary syndromes, some CAC
was detected, with a substantially greater score than in matched control
subjects without coronary artery disease [70].
CAC score has been shown to have a high prognostic power being
associated with hard cardiac events and total mortality in follow up
studies. While the zero calcium score was associated with very low
event rate <0.03% per year in metaanalysis studies [71], the hazard ratio
for major coronary events went up to 3.89 and 7.1 in patients with CAC
score between (1-100) and (101-300), respectively when compared to
individuals without calcium [72].
It is worth noting that in spite of the relationship between CAC and
plaque burden, there is only a weak correlation between the amount of
CAC and the angiographic stenosis severity. Large amounts of CAC
are not necessarily associated with the presence of signicant stenoses.
Even the absence of CAC, though makes the presence of signicant
stenosis relatively unlikely, zero calcium score cannot be used to rule
out coronary stenoses in symptomatic individuals, especially when
they present at young age and with acute symptoms [73].
Detection of Vulnerable Plaque in Asymptomatic
Vulnerable Subjects
Te current appropriateness criteria do not recommend using
computed angiography as a screening tool in asymptomatic population
considering the risk of radiation and contrast media, cost and lack of
supporting evidence. Motoyama et al. studied 1059 asymptomatic
subjects by MDCT where atherosclerotic plaques were analyzed for the
presence of the three vulnerability features; the plaque characteristics of
lesions resulting in ACS during the follow-up of 27 10 months were
evaluated. It was shown low attenuation and/or positive remodeling
independently predicted ACS (hazard ratio=22.8, CI=6.975.2,
p<0.001) with a signicantly higher likelihood of ACS than 2 feature-
negative plaques or no plaques (p<0.001) [74].
Since HIV patients show high rates of MI and sudden cardiac
deaths, a recent study has assessed the plaque vulnerability in
asymptomatic relatively young HIV-infected subjects versus non-
HIV-infected controls who were cardiovascular risk matched. Te
study concluded that the HIV-infected group has higher prevalence of
Study Type of plaque and its measured attenuation value
Shroeder et al. 2001 [50]
Soft: 14 26 HU
Intermediate: 91 21 HU
Calcifed: 419 194 HU
Rasouli 2006 [51]
Soft: 23 71 HU
Fibrous: 108 79 HU
Fibro-calcifed: 299 112 HU
Calcifed: 404 264 HU
Motoyama et al. 2007 [52]
Soft: 11 12 HU
Fibrous: 78 21 HU
Calcifed: 516 198 HU
Pohle et al. 2007 [53]
Hypo-echogenic: 58 43 HU
Hyper-echogenic: 121 34 HU
Table 2: MDCT studies showing attenuation values of different coronary plaques
types.
CT parameter Correlation P value
Histology
calcifcation r
2
=0.74 <0.001
Fibrous tissue r
2
=0.76 <0.001
Lipid core size r
2
=0.24 <0.002
Lipid core size (after excluding calcium) r
2
=0.81 <0.001
IVUS
Necrotic core % r=- 0.539 <0.001
Fibrous tissue % r=0.571 <0.001
Fibrofatty tissue % r=- 0.074 =0.512
Calcifcation % r=- 0.113 =0.316
Table 3: Summary of studies showing correlation between different CT plaque
densities and histology or IVUS [50-53,59-64].
Citation: Youssef G, Budoff M (2013) Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it
Stand Among Others? Angiol 1: 111. doi: 10.4172/2329-9495.1000111
Page 6 of 8
Volume 1 Issue 2 1000111
Angiol
ISSN: 2329-9495 AOA, an open access journal
subjects with one or more vulnerability criterion, Moreover; there was
a signifcantly higher number of low attenuation plaques and positive
remodeling per subject [75].
Technical Limitations of CTCA
As previously highlighted in table 1, some technical factors might
afect the role of CTCA in characterization of coronary plaques.
Tese limitations include: 1) Radiation exposure; typical efective
dose of radiation for retrospectively gated reconstruction is about 15
mSv, radiation doses delivered have markedly reduced to less than 2
mSv with the advent of newer prospective gating and ultra-low-dose
protocols, these advances in technology are expected to further expand
the CTCA applications and would permit follow-up studies to evaluate
the progression of atherosclerotic plaques over time and with the use
of interventional drugs like statins. 2) contrast agents; currently used
contrast media in CTCA are considerably safe, however, there is a
minimal risk that should be anticipated and dealt with in patients with
contrast allergy or those with advanced renal insufciency. 3) artifacts;
various CT artifacts could limit the accuracy of CTCA in studying the
plaque composition. Of note, dense calcifcation is a major limiting
factor that could result in the blooming artifact phenomenon where
calcium looks bigger than it actually is and 4) the signifcant overlap
between tissue densities as previously discussed, rendering the accurate
defnition of plaque constituents more challenging [76].
Future Perspectives and Conclusions
Te concept of vulnerable plaque has been introduced with the
intention of detection of those high risk plaques that are potentially
capable of causing acute cardiac events. Further risk stratifcation of
asymptomatic or previously assumed low risk population is a complex
process that goes far and beyond the mere use of risk score calculators
or blood biomarkers. Tis process has been recently supported by
the rapidly advancing imaging modalities that have shown some
capabilities in visualizing various physical, chemical and biological
aspects of atherosclerotic plaques that could defne their vulnerability.
Among non-invasive modalities, MDCT seems to have the
highest possibility of fulflling the expectations of researchers and
clinicians. In addition to its role in assessment of signifcant coronary
obstruction with excellent diagnostic accuracy, it is getting popular
as a promising non-invasive tool in detection of vulnerable features.
Tis has been supported by studies that showed MDCT to have a good
diagnostic accuracy and correlation when compared to histology and
IVUS.A bigger role is expected from MDCT with the development of
higher resolution scanners with lower radiation dose and the use of
novel contrast media that could be targeted towards specifc plaque
constituents.
A major question afer the identifcation of a vulnerable coronary
plaque, should it be treated and how? At present there are no data to
prove that interventional treatment strategies for those high risk but
asymptomatic plaques are superior to conventional medical treatment.
Data from large prospective studies will be needed to determine which
approach will be benefcial.
Finally, we always should remember looking at the big picture
accepting the idea that the pathogenesis of ACS does not involve only
factors operating at the plaque level, but rather there is a concurrence of
local and extra-coronary factors that involve coagulation, neuroendocrine,
infammatory and immune response of the vascular tissue.
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